Edited by Spaska Angelova Stanilova .

276 pages .Open Access .

Recently, it has been a great challenge to acquire an in-depth knowledge in regards to the inner workings and interactions between the immune system and environmental factors along with their impact on human health.

Environmental factors like growing pollution, changes in lifestyle habits, dietary components, as well as various microorganisms are interfering with components of our immune system driving a normal immune response to hyper- or hypo-reactivity.

When the immune system becomes hyper-reactive it targets one’s own healthy cells leading to the destruction of tissues in the body, a process which is known as the onset of autoimmune disease. The common target organs include the thyroid, adrenal, stomach, liver, pancreas, kidneys, skin, joints, muscles and the nervous system. The organ specific autoantibodies often occur together with non-organ specific antibodies such as anti-DNA and anti-nucleoproteins in Systemic Lupus Erythematosus (SLE).

Autoimmune disorders are known to affect a substantial number of people worldwide, demonstrating a gender bias and it is the second largest cause of chronic illness. They represent the fifth leading cause of death among women in age groups up to 60.

The main feature of the human immune system is the fine discrimination between self components from foreign antigens. Immunological tolerance is a state of unresponsiveness induced by prior exposure to a particular antigen, mostly self antigens. Thus, the body must establish self-tolerance mechanisms in order to avoid reactivity towards self components.

One theory explains that breaking of self-tolerance is when some microorganisms (such as bacteria or viruses) or xenobiotics trigger the changes in immune regulation which results in autoimmune disorders. Recognition of the molecular pattern of a pathogen, which is istinguishable from the host molecules is important for protective immune response and when mistaken, could often lead to autoimmunity. This process strongly depends on the individual genetics background in a person. Certain individuals are genetically susceptible to developing autoimmune diseases. There are a number of genes that may plausibly be involved in the development of autoimmunity. It is known that genetics predisposition is associated with three main sets of genes, including immunoglobulins, T-cell receptors and major histocompatibility complex (MHC), but are not restricted to them. The development of autoimmunity is also strongly influenced by inherited disease-associated single nucleotide polymorphisms rather than deletion or rearrangements. Cytokine, cytokine receptors and TLR-associated genes have recently attracted great interest as candidate genes for autoimmune diseases. Over the past decade there has been great interest in testing candidate gene polymorphisms for evidence of their association with various autoimmune diseases. The genetic hallmarks of autoimmunity are undoubted, however particular genes and triggering intracellular signaling pathway remains elusive. Genes of cytokine and immune cell receptors regulating function of immune system are expressed under control of intracellular signaling pathway such as TLR signaling pathway, Fc receptors, receptors and ligands of immunological synapses, vitamin D receptors and other immune related genes.

Two opposite hypothesis are currently under investigation. One of them (hygiene hypothesis) discusses whether the reduced exposure to certain infections, as a result of improved hygiene and living conditions, may be responsible for the increased incidence in autoimmune conditions. The other hypothesis is that autoimmune diseases might be a consequence of post-infections conditions. Despite this contradiction, infection agents and their antigens obviously play a pivotal role in the development of autoimmunity through interaction with the immune system. Arguments that support the role of infection in specific autoimmune diseases come from clinical, epidemiological and laboratory studies. New data demonstrates that the gut flora compositions can also influence the development of autoimmune diseases. For example, the use of probiotics containing lactobacilli decreases the incidence of diabetes in NOD mice. At the same time, a range of differing factors such as dietary supplements, hormones, alcohol consumption, vitamins and drugs, cigarette smoking, etc. implicated in autoimmune disease onset. Dietary antigens also stimulate antigen receptors and aberrant immune response can progress to autoimmunity.

According to the afore discussed, it seems obvious that neither genetic predisposition nor environmental factors alone are sufficient to cause the disease. The triggering factors and intracellular signaling pathway crosstalk are currently under extensive investigation with high hopes for revealing the autoimmunity clue.

In conclusion, autoimmune diseases develop in genetically predisposed organisms as a result of a specific triggering agent (infectious or noninfectious), causing dysfunction in the immune system activity with subsequently developed abnormal autoimmune mechanism affecting its own cells and tissues of the organism.

This book attempts to seize the new opportunities for moving research forward, leading to a new approach for the prevention and treatment of autoimmune diseases. The first section of this book is focused on genes, gene expression and signaling pathways involved in autoimmune pathogenesis. The second one attempts to present current data for interaction of microbiota with human immune system, which are implicated in the development of autoimmune disease.

We hope the book will be useful for anyone wanting to expand their knowledge of the occurrence and mechanisms of autoimmunity.